AI Article Synopsis
- Endotoxin tolerance can dampen neutrophil responses to Toll-like receptor (TLR) agonists, but its specific effects on neutrophils were not well understood.
- Prolonged exposure to lipopolysaccharide (LPS) led to tolerance, reducing certain intracellular signaling and respiratory burst activities in neutrophils, which wasn't altered by GM-CSF pretreatment.
- Despite these changes, tolerized neutrophils continued to produce CXC chemokine ligand 8 and maintained a proinflammatory behavior, while also showing delayed apoptosis when responding to survival factors.
Article Abstract
Endotoxin tolerance has the potential to limit phagocyte responses to Toll-like receptor (TLR) agonists, but the role of tolerance in regulating neutrophil responses is unknown. We investigated neutrophil responses to prolonged lipopolysaccharide (LPS) exposure and observed induction of tolerance in intracellular signaling pathways and respiratory burst. These effects were not prevented by granulocyte macrophage-colony stimulating factor (GM-CSF) pretreatment, and tolerized neutrophils retained the ability to respond to GM-CSF and other survival factors with a delay in apoptosis. In addition, LPS-exposed neutrophils showed continued generation of CXC chemokine ligand 8, which was not reduced in tolerized cells. Induction of tolerance was associated with a loss of TLR4 surface expression. Tolerance, therefore, induces a selective reprogramming of neutrophil function, but cells retain a predominantly proinflammatory phenotype.
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| http://dx.doi.org/10.1189/jlb.0405236 | DOI Listing |
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